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Efforts in Anticancer Drug Exposure Research

Dr. Makiko Sasaki,
Professor of Public Health and Basic Nursing Studies, Akita University Graduate School of Medicine and Faculty of Medicine

Research regarding exposure to anticancer drugs has been performed primarily on the effects on the health of medical personnel due to occupational exposure, the detection of anticancer drugs in the urine, and the conditions of contamination of anticancer drugs in a hospital environment. Below, I will introduce examples of each of these types of research.

1. Research Regarding the Health Effects Caused by Occupational Exposure to Anticancer Drugs

As a method of clarifying the health effects caused by exposure, genotoxicity testing, including chromosomal aberration and DNA damage, and studies regarding the incidence of the disease and development of subjective symptoms, etc. have been performed.

With regard to the health effects on medical personnel, it has been reported in 1979 by Falck K. et al. 1)
that activity of mutagens in the urine of nurses handling anticancer drugs was significantly higher than controls, and subsequently, various research has been performed to validate this. In a study of nurses and pharmacists who have handled anticancer drugs, it has been reported that exposure to anticancer drugs has a significant relationship with miscarriages and the total number of miscarriages and stillbirths (Valanis B. et al.2)
) Moreover, it has also been reported that the odds ratio of premature birth and low-weight babies for nurses who are exposed frequently to anticancer drugs is significantly higher than for the control group of nurses (Fransman W. et al. 3)
) In retroactive pregnancy results and results analyzing occupational exposure of 7,482 of the 8,461 participants in the Nurse’s Health Study II in the United States, approximately 10% of the nurses giving birth had spontaneous abortions (less than 20 weeks), and the risk of spontaneous abortion doubles for nurses who had been exposed to antineoplastic agents (Lawson C. et al. 4)
) It has also been reported that nurses handling anticancer drugs have significantly higher levels of DNA damage than the control group5)
. As a result of checking the level of DNA damage of nurses handling anticancer drugs to investigate the health effects on Japanese nurses caused by handling the anticancer drugs, the authors obtained a result indicating that the level of DNA damage to the nurses was significantly higher than the control group of office employees 6)
. It suggested that DNA damage may be caused by handling anticancer drugs in Japanese nurses handling anticancer drugs as well. In recent reports, it has been reported that nurses and pharmacists handling anticancer drugs have significantly higher aberrations of chromosomes 5, 7, and 11, which are thought to be related to myelodysplastic syndrome and the onset of acute leukemia, than the nurses and pharmacists who do not handle anticancer drugs (McDiarmid MA. et al. 7)
). Based on the above, there is sufficient reason to fear the effects on the health of medical personnel of handling anticancer drugs, such as DNA damage and chromosomal aberrations as well as its effects on birth.

2. Environmental and Biological Monitoring

In 1984, Hirst et al. 8)
reported that the anticancer drug cyclophosphamide was detected in the urine of nurses handling anticancer drugs. In 1992, Sessink P.M.J. et al. 9)
took swabs of various locations including the pharmacy and outpatient departments of the hospital, the floors of the hospital wards with cancer patients, and cabinets and tables where drugs were prepared, and at the same time, detected anticancer drugs in the urine of pharmacists and nurses. Although there were differences in whether or not drugs were detected and in the detected amounts, the results suggested environmental contamination due to anticancer drugs and exposure to anticancer drugs of medical personnel. Contamination in the environment of anticancer drugs varies based on techniques used and protective measures when handling them; however, even in Japan, Sugiura S. et al. 10)
have reported the detection of cyclophosphamide on tables on which anticancer drugs were mixed and prepared and its surroundings, on the surfaces of telephone stands and bedside tables and under IV drip stands, and that cyclophosphamide was detected in the urine of nurses who had not mixed and prepared anticancer drugs and physicians who had mixed and prepared anticancer drugs at the same hospital. Even in the results of research performed by the authors 11)
, anticancer drugs were detected in the urine of nurses who did not mix or prepare them. Even if the exposure is extremely small, it is a fact that the risk to health is high for long-term exposure to drugs recognized to be carcinogenic, such as cyclophosphamide.

Further research to thoroughly ascertain the environmental contamination conditions leading to opportunities for exposure is required.

3. Detection of Anticancer Drugs in Urine and in the Environment Made Possible in Japan

Monitoring of environmental contamination conditions caused by anticancer drugs and anticancer drugs in the urine of medical personnel is important to clarify the relationship between exposure and the health effects on medical personnel and others as well as to validate the effectiveness of protective measures and to create appropriate protective measure guidelines.

However, to detect anticancer drugs in urine and in the environment, qualitative analysis devices requiring specialist knowledge and skills were required, and when this knowledge and skills were not available, often requests were made to overseas testing agencies. At that time, efforts to research to clarify the current conditions encountered many difficulties, including the large amount of monetary expense required for analysis. However, in recent years, a sampling method to detect exposure of anticancer drugs in the environment has been developed in Japan as well by Shionogi Analysis Center Co., Ltd. (http://www.shionogi-ac.co.jp/products/environment/index.html
). Analysis of anticancer drugs in urine can now be performed at this same center. It has already reported research results 12-13)
, and has become familiar in research efforts. The details regarding its use are noted on the company’s website, so please be sure to reference it. As monitoring methods have become more familiar, research regarding the current conditions of exposure based on various medical information in Japan has also become possible. In future, I look forward to further advancement in the accumulation of data that will be evidence for exposure protection measures and the management of the health of people concerned.